山奈酚与水的氢键作用对其抗氧化活性影响的理论研究

本文用密度泛函理论在(RO)B3LYP/6-31G(2d,2p)水平上对山奈酚及其与水分子之间形成的氢键复合物进行结构优化,通过热力学计算研究了不同位置的酚羟基发生抽氢反应的键离解能(BDE)、质子解离反应过程的质子解离能(DPE)受分子间氢键的影响。结果表明:与H2O形成的分子间氢键会影响化合物结构,改变化合物B环与AC环的二面角,A5位酚羟基更容易发生抽氢反应和质子解离反应,此位点的BDE和DPE均明显降低,同时也降低C3位质子解离的DPE。分子间氢键的形成促使酚羟基的抽氢和质子解离反应,提高化合物抗氧化活性。     

Development of a noncompetitive phage anti-immunocomplex assay for brominated diphenyl ether 47

We present a new application of the noncompetitive phage anti-immunocomplex assay (PHAIA) by converting an existing competitive assay to a versatile noncompetitive sandwich-type format using immunocomplex binding phage-borne peptides to detect the brominated flame retardant, brominated diphenyl ether 47 (BDE 47). Three phage-displayed 9-mer disulfide-constrained peptides that recognize the BDE 47-polyclonal antibody immunocomplex were isolated. The resulting PHAIAs showed variable sensitivities, and the most sensitive peptide had a dose-response curve with an SC₅₀ (concentration of analyte producing 50% saturation of the signal) of 0.7 ng/ml BDE 47 and a linear range of 0.3-2 ng/ml, which was nearly identical to the best heterologous competitive format (IC₅₀ of 1.8 ng/ml, linear range of 0.4-8.5/ml). However, the PHAIA was 1400-fold better than homologous competitive assay. The validation of the PHAIA with extracts of house furniture foam as well as human and calf sera spiked with BDE 47 showed overall recovery of 80-113%. The PHAIA was adapted to a dipstick format (limit of detection of 3.0 ng/ml), and a blind test with six random extracts of local house furniture foams showed that the results of the PHAIA and dipstick assay were consistent, giving the same positive and negative detection.     

BDE 49 and developmental toxicity in zebrafish

The polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants. Human health concerns of these agents have largely centered upon their potential to elicit reproductive and developmental effects. Of the various congeners, BDE 49 (2,2',4,5'-tetrabromodiphenyl ether) has been poorly studied, despite the fact that it is often detected in the tissues of fish and wildlife species. Furthermore, we have previously shown that BDE 49 is a metabolic debromination product of BDE 99 hepatic metabolism in salmon, carp and trout, underscoring the need for a better understanding of biological effects. In the current study, we investigated the developmental toxicity of BDE 49 using the zebrafish (Danio rerio) embryo larval model. Embryo and larval zebrafish were exposed to BDE 49 at either 5 hours post fertilization (hpf) or 24 hpf and monitored for developmental and neurotoxicity. Exposure to BDE 49 at concentrations of 4iμ-32 μM caused a dose-dependent loss in survivorship at 6 days post fertilization (dpf). Morphological impairments were observed prior to the onset of mortality, the most striking of which included severe dorsal curvatures of the tail. The incidence of dorsal tail curvatures was dose and time dependent. Exposure to BDE 49 caused cardiac toxicity as evidenced by a significant reduction in zebrafish heart rates at 6 dpf but not earlier, suggesting that cardiac toxicity was non-specific and associated with physiological stress. Neurobehavioral injury from BDE 49 was evidenced by an impairment of touch-escape responses observed at 5 dpf. Our results indicate that BDE 49 is a developmental toxicant in larval zebrafish that can cause morphological abnormalities and adversely affect neurobehavior. The observed toxicities from BDE 49 were similar in scope to those previously reported for the more common tetrabrominated congener, BDE 47, and also for other lower brominated PBDEs, suggest that these compounds may share similarities in risk to aquatic species.     

2,2′,4,4′,5‐Pentabromodiphenyl ether induces lipid accumulation throughout differentiation in 3T3‐L1 and human preadipocytes in vitro

Flame retardants, specifically polybrominated diphenyl ethers (PBDEs), are chemical compounds widely used for industrial purposes and household materials. NHANES data indicate that nearly all Americans have trace amounts of PBDEs in serum, with even higher levels associated with occupational exposure. PBDEs are known to bioaccumulate in the environment due to their lipophilicity and stability, and more importantly, they have been detected in human adipose tissue. The present study examined whether the PBDE congener, BDE‐99 (2,2′,4,4′,5‐pentabromodiphenyl ether; 0.2‐20 μM), enhances the adipogenesis of mouse and human preadipocyte cell models in vitro via induced lipid accumulation. 3T3‐L1 mouse preadipocytes and human visceral preadipocytes demonstrated enhanced hormone‐induced lipid accumulation upon BDE‐99 treatment. In addition, BDE‐99 (20 μM) induced preadipocyte differentiation and lipid development in nondifferentiated human preadipocytes. BDE‐99, the second most abundant congener in human adipose tissue, increased total lipids in differentiating adipocytes and therefore showed a potential role in the regulation of adipogenesis. This warrants more research to further understand the impact of lipophilic persistent pollutants on adipose tissue homeostasis.     

The effect of catechol O-methylation on radical scavenging characteristics of quercetin and luteolin--a mechanistic insight

The biological effect of flavonoids can be modulated in  vivo due to metabolism. The O-methylation of the catechol group in the molecule by catechol O-methyl transferase is one of the important metabolic pathways of flavonoids. In the present study, the consequences of catechol O-methylation for the pH-dependent radical scavenging properties of quercetin and luteolin were characterized both experimentally and theoretically. Comparison of the pKa values to the pH-dependent TEAC profiles reveals that O-methylation not only affects the TEAC as such but also modulates the effect of changing pH on this radical scavenging activity due to an effect on the pKa for deprotonation. The pH-dependent TEAC curves and computer calculated electronic parameters: bond dissociation energy (BDE) and ionisation potential (IP) even indicate that O-methylation of the luteolin catechol group affects the radical scavenging potential only because it shifts the pKa for deprotonation. O-Methylation of the quercetin catechol moiety affects radical scavenging capacity by both an effect on the pKa, and also by an effect on the electron and hydrogen atom donating properties of the neutral (N) and the anionic (A) form of the molecule. Moreover, O-methylation of a catechol OH-group in quercetin and luteolin has a similar effect on their TEAC profiles and on calculated parameters as replacement of the OH-group by a hydrogen atom. Altogether, the results presented provide new mechanistic insight in the effect of catechol O-methylation on the radical scavenging characteristics of quercetin and luteolin.     

Quantum mechanical study of antioxidative ability and antioxidative mechanism of rutin (vitamin P) in solution

A quantum mechanical approach has been used to shed light on the antioxidative mechanism for scavenging hydroxyl radicals (OH) and superoxide radicals () by rutin in the solution phase. Density-functional theory (DFT) using B₃LYP and UB₃LYP functional and split-valance 6-311+G^∗∗ basis sets were used to optimize rutin and its different radical forms. Analysis of the theoretical bond dissociation enthalpy (BDE) values for all OH sites of rutin in solution clearly shows the importance of the B-ring and the 3′-OH and 4′-OH groups in the antioxidant activity. We have also investigated the spin density of the radicals to determine the delocalization possibilities. The results of the calculations showed that the oxidation of rutin by both the hydroxyl radical and superoxide radical is an exothermic reaction. In all calculations solvent effects were considered using a polarized continuum model (PCM).     

Butein: From ancient traditional remedy to modern nutraceutical

Butein (2′,3,4,4′-tetrahydroxychalcone), a simple chalcone derivative, occurs in many unrelated genera including Butea Dahlia, Coreopsis and Searsia. It is a reputed food additive and a common ingredient of botanicals used in herbal medicine formulations, particularly in Asian countries. Although a simple polyphenol, this molecule exhibits a range of pharmacological properties, most notably acting as a potent protein tyrosine kinase inhibitor and as an antineoplastic agent. Researchers have convincingly demonstrated that butein inhibits the epidermal growth factor receptor in HepG2 cells and the tyrosine-specific protein kinase activities of the epidermal growth factor receptor. In addition, it also exhibits promising anti-inflammatory, antidiabetic, antinephritic, antithrombin, anti-angiogenic and hepatoprotective activities in various animal models. Although this molecule is endowed with an impressive list of biological properties, which have acted as scientific support for its commercialization, there are no review articles that coherently discuss various aspects of this chalcanoid. This review aims to explore the pharmacological relevance of butein, together with its structure–activity relationships and mechanisms of action. In addition, the occurrence, chemical synthesis and biosynthesis of butein are discussed.     

Oxidation of hydroquinones by a nonheme iron(IV)-oxo species

The reactivity of an isolated, well-characterized nonheme iron(IV)-oxo complex, [(TMC)Fe^IVO]²⁺ (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), has been examined in the oxidation of hydroquinones. This complex has been shown to oxidize a series of hydroquinones, resulting in the production of the corresponding quinone products. Kinetic studies performed with substituted hydroquinones revealed a good correlation between reaction rates of the iron(IV)-oxo complex and the electron-donating ability of the substituents and the bond dissociation energy (BDE) of substrate O-H bonds. These results with a kinetic isotope effect (KIE) of 2.7 led us to propose a hydrogen-atom abstraction mechanism for the oxidation of hydroquinones by the nonheme iron(IV)-oxo species.